title: Effects of accelerated senescence on learning and memory, locomotion and anxiety-like behavior in APP/PS1 mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is characterized by a deficit in motor and spatial learning-memory and alteration of non-cognitive behavior. The generation of transgenic mice with presence of AD pathologies that cause learning and memory deficits has led to improved understanding of the behavioral and pathophysiological processes underlying AD. A novel APP/PS1 mouse model in the senescence accelerated mouse prone 8 (SAMP8) background--SAMP8 APP/PS1 was generated. To assess the behavioral and other AD-related changes in this SAMP8 APP/PS1 model, the present report covers a phenotypical analysis of this model for working memory, spatial memory, motor performance and anxiety-like behavior. SAMP8 APP/PS1 mice showed motor and spatial memory impairments, together with an increase of locomotor activity and lower anxiety-like behavior at 9months old. In contrast, C57 APP/PS1 and SAMP8 wild type mice were inconspicuous in all of these tasks and properties except C57 APP/PS1 mice which showed motor memory impairment in the shuttle box task at 9 months old. Standard senescence-associated beta-galactosidase (SA-beta-GAL) staining and amyloid beta (Aβ) immunohistochemistry showed more severe pathological changes in the SAMP8 APP/PS1 mice. SAMP8 APP/PS1 mice exhibited earlier deficits in their non-cognitive and cognitive behaviors which are coincident in the AD patient and the results suggest that this new type of mice might be a better model for studying the age-related dementia of the Alzheimer type and for assessing the potential therapeutic agents for AD.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 200240 Shanghai, China.
authors.forename: Kenghoe
authors.initials: K
authors.lastname: Lok
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: He
authors.forename: Hanlin
authors.initials: H
authors.lastname: Shen
authors.forename: Zejian
authors.initials: Z
authors.lastname: Wang
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
mesh_terms: D000375:Aging / Q000235:genetics*; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001007:Anxiety / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000502:physiology; D005106:Exploratory Behavior; D020233:Gait Disorders, Neurologic / Q000209:etiology* / Q000235:genetics; D005838:Genotype; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology* / Q000235:genetics; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: AD; APP; APP/PS1; Alzheimer's disease; Anxiety; Aβ; CS; Learning–memory; Locomotor; NFTs; PS1; PS2; SAMP8; Senescence; TBS; UCS; amyloid beta; amyloid precursor protein; conditioned stimulus; neurofibrillary tangles; presenilin 1; presenilin 2; senescence accelerated mouse prone 8; tris-buffered saline; unconditioned stimulus